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A viral capsid assembled in a X-ray beam

The simplest viruses are made of a protein shell – the capsid – enclosing the genetic code of the virus – the genome – as DNA or RNA. Among these viruses, Noroviruses are the first cause of non bacterial gastroenteritis in humans and animals. Their capsid, the diameter of which varies around 40 nm, is made up of 180 copies of a single structural protein arranged into a icosahedron, i.e. a solid with 20 triangular faces and 12 vertices. Remarkably, these proteins are capable of self-assembling reversibly in vitro, without the genome or any cellular components, by the interplay of the solution pH and the ionic strength. The molecular mechanisms remain unknown to date and the nature of the intermediate species is much debated. Yet, except the obvious benefit that would bring the knowledge of such mechanisms to virology and to the development of anti-viral treatments, the self-assembly of viral proteins may find applications in nanomedicine in view of using the capsid as vector of either magnetic particles for medical imaging or therapeutic molecules, towards specifically targeted tissues.


The self-assembly kinetics of viral capsids is a multiscale process that requires to probe heterogeneous molecular species with nanometer sizes over timescale ranging from milliseconds to hours. In collaboration with biologists from the Laboratoire de Virologie Moléculaire et Structurale in Gif-sur-Yvette, we have studied the self-assembly of a Norovirus capsid by time-resolved small-angle X-ray scattering with the synchrotron sources SOLEIL and ESRF. Thanks to ad hoc algorithms for data processing, we have extracted and reconstructed for the first time the structure of an intermediate species that plays a pivotal role in the assembly process. It turns out that initial protein dimers combine in a few tens of seconds to yield an intermediate made of two pentamers of dimers connected by an interstitial dimer. Due to a strong cooperativity, six of these intermediates are associated to form an icosahedral capsid in several tens of minutes. We believe that the large difference between the timescales of both steps and the interlocking shape of the intermediates might confer an enhanced robustness to the system in regards of kinetic traps and misassembly.


Kinetic scheme for the self-assembly of a Norovirus capsid. The free dimers (magenta) are rapidly associated in two pentameric units (blue) connected by an interstitial dimer (red). These intermediates are then slowly combined – likely by interlocking with each other and by involving free dimers – to form a hollow capsid.


Reference :

Norovirus Capsid Proteins Self-Assemble through Biphasic Kinetics via Long-Lived Stave-like Intermediates
Guillaume Tresset, Clémence Le Coeur, Jean-François Bryche, Mouna Tatou, Mehdi Zeghal, Annie Charpilienne, Didier Poncet, Doru Constantin, and Stéphane Bressanelli
J. Am. Chem. Soc. 135, 15373–15381 (2013)
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